Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD

Purpose: Current guidelines support using in combination more than one class of tong-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD. Methods: COPD patients (mean FEV1 1.37 L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15 mu g BID [n = 76] or tiotropium 18 mu g QD [n = 80]), or combined therapy (sequential dosing of arformoterol 15 mu g BID and tiotropium 18 mu g QD [n = 78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes. Results: Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10 L) and tiotropium (0.08 L) treatment groups and greater for the combined therapy group (0.22 L; all p-values < 0.005). Peak FEV1, peak FVC, 24-h trough FEV1, and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values < 0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events. Conclusion: In this study, the combination of nebulized arformoterol 15 mu g BID plus tiotropium 18 mu g DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated. (c) 2009 Elsevier Ltd. All rights reserved.